Our studies of gyrate atrophy of the choroid and retina are aimed at understanding the genetic heterogeneity, pathophysiology, treatment and metabolic ramifications of this disorder. We are using clinical somatic cell genetic and immunologic techniques to elucidate possible differences in the mutant genes which lead to the gyrate atrophy phenotype. Our studies of pathophysiology include enzymatic and substrate measurements in human ocular tissues; screening of visually-impaired animals for a disorder analogous to GA; and the study of several in vitro cell culture models (using GA fibroblasts and myocytes and chick retinal pigmentary epithelium). We are also conducting long-term clinical studies of treatment of GA. Primarily this involves the use of an arginine-deficient diet to correct the biochemical abnormalities of GA patients. Various pharmacologic agents which increase daily losses of arginine and/or ornithine are also under investigation. Preliminary results suggests that the chorioretinal degeneration does not progress following biochemical correction and that vision may actually improve modestly. We are also interested in the delineation and explanation of various secondary metabolic disturbances in gyrate atrophy patients.